Ventricular dysfunction frequently persists after open heart surgery in infants and children. The cause of postoperative contractile failure in this age group is often unclear, but is sometimes attributed to inadequate intraoperative myocardial protection. Thyroid hormone regulates contractile function postoperatively in adults. This phenomenon has not been examined in the immature heart, though cardiac dysfunction relates to drops in thyroid levels induced by cardio- pulmonary bypass in children. We postulate that these disturbances in thyroid hormone homeostasis disrupt mitochondrial function and maturation in the developing heart in vivo. Deficiencies in specific mitochondrial membrane proteins then limit the ATP production and supply necessary for contractile processes. Preliminary data obtained in our laboratory indicate that thyroid hormone deficiency does alter mitochondrial maturation and respiratory control in vivo. These alterations occur concurrently with decreased expression of a major mitochondrial membrane protein, the adenine nucleotide translocator. We propose defining maturational events related to thyroid regulation of mitochondrial maturation in vivo. Subsequently, we will determine the importance of these events in a neonatal model, which emulates clinical cardiopulmonary bypass, ischemia, and reperfusion. Finally T3 supplementation during surgery will be tested as a mode to improve postoperative cardiac function by effecting these mitochondrial mechanisms. Novel magnetic resonance spectroscopy techniques performed in sheep in vivo will be a principal investigative tool, used in conjunction with metabolic and molecular biology techniques. This integrative approach has previously proved effective in delineating previously unrecognized mitochondrial events related to maturation, ischemia and cardiopulmonary bypass. Specific aims are: 1 a) Define and characterize thyroid effect on maturation myocardial respiratory control in vivo; b) Characterize thyroid effects on cardiac mitochondrial biogenesis using two mitochondrial proteins the adenine nucleotide translocator (ANT) and beta-F1-ATPase as reporters. 2 a) Determine if TH acutely stimulates myocardial function and mitochondrial respiration following ischemia associated with circulatory arrest and bypass; b) Determine longer term effects of thyroid stimulation on energy metabolism, mitochondrial biogenesis and their relation to contractile function following cardiac ischemia in the developing heart.